PROJECT SUMMARY/ABSTRACT Few Americans were untouched by the Great Recession (GR). Though one might expect major economic downturns such as this to negatively affect physical health, the evidence is, in fact, mixed. This project will integrate biologically-informed empirical methods with uniquely rich longitudinal data at the individual and local market level to test hypotheses about the effects of economic stress from the GR on cardiovascular disease (CVD) risk factors and events. Six waves of CVD risk factors and validated CVD events from the Multi-Ethnic Study of Atherosclerosis (MESA) collected before and after the GR will be linked with detailed time-varying area- and demographic-specific measures of local labor and housing market conditions. The first four waves of MESA, collected between mid-2000 and mid-2007, before the onset of the GR in 2008, will be used to estimate individual-specific aging trajectories. The fifth wave, collected in 2010 through 2012 immediately post GR, and the sixth wave, collected in 2016 and 2017, will be used to investigate both short and longer-term effects of the Recession beyond the expected age-related changes that we allow to differ for each individual. Specific aims of this project are to: (1) test hypotheses about effects of exposures to different sources of economic stress on six major biological risk factors for CVD, controlling for individual-specific trajectories of biology, exploiting plausibly exogenous variation in the severity of the GR and post-recession recovery to isolate causal effects. This includes, for example, comparing effects of changes in housing market conditions on those who owned homes pre-Recession vs. those who did not. (2) test biologically informed hypotheses about the timing and persistence of these effects across systems; (3) test whether GR effects on biological risk factors are reflected in increased rates of CVD events ? a hard clinical outcome; (4) test whether potential pathway variables: health behaviors, health insurance, medication use (anti-hypertensives, diabetes medications, and statins), depression, and social support changed with the economic stresses of the GR; and (5) measure CRP levels in stored plasma from MESA for this research and for future use by the entire research community. Integrating insights from biology and economics, this project will provide new, credible evidence on the causal effects of economic conditions on health by leveraging unique strengths of MESA to test biologically informed hypotheses regarding differential impacts of the GR on different biomarkers over time, using innovative models that control for individual-specific aging trends in biology, while exploiting variation in economic stress across population sub-groups from differential exposures to the unanticipated changes in local housing and labor markets. Empirical estimates from this work of the magnitude of health impacts of varying levels of economic stress will provide a comprehensive and credible body of evidence on the causal impacts of economic upheavals on health outcomes in the U.S. population.